Phase I Cetuximab and Concurrent Radio-chemotherapy

Non-small Cell Lung Cancer Clinical Trial

Official title:

Determination of the Toxicity of Standard Dose Cetuximab Together With Concurrent Individualised, Isotoxic Accelerated Radiotherapy and Cisplatin-vinorelbine for Patients With Stage III Non-small Cell Lung Cancer: A Phase I Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00522886
• Other study ID #: 07-03-009
• Status: Completed
• Phase: Phase 1
• First received: August 29, 2007
• Last updated: July 18, 2011
• Start date: April 2007

Study information

• Verified date: July 2011
• Source: Maastricht Radiation Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

To determine the MTD toxicity of standard dose cetuximab together with concurrent individualized, isotoxic accelerated radiotherapy and cisplatin-vinorelbine

Description:

Phase I trial with escalating doses of vinorelbine and standard doses of radiotherapy, cisplatin and cetuximab.

Eligible patients receive 2 cycles of carboplatin (AUC 5) day 1 and gemcitabine (1250 mg/m2) days 1,8. One cycle duration is 21 days.

Patients without progressive disease (PD) according to the RECIST criteria (appendix 1) will be entered in the phase I dose-escalation part of the study. Chest radiation is given concurrently with cetuximab, cisplatin and vinorelbine. The latter drug will be escalated in three steps until dose-limiting toxicity occurs.

On day 43, i.e. 14 days after the last gemcitabine delivery, radiotherapy is started.

Radiotherapy: In all patients in every dose-step, the radiation will be given as follows:

first 3 weeks: 1.5 Gy BID to a dose of 45 Gy in 30 fractions, then 2 Gy QD to a mean lung dose (MLD, this is related to radiation-induced lung damage) of 19 Gy. Maximum dose: 69 Gy given in 5.5 weeks. Maximum dose to the spinal cord: 50 Gy.

Cetuximab: All patients will receive a starting dose 400 mg/ m2 7 days before the beginning of radiotherapy (i.e. day 36), thereafter a weekly dose 250 mg/ m2 during the course of radiotherapy for 5 consecutive weeks. Cetuximab will be delivered at the same days as chemotherapy.

Cisplatin: In all patients in every dose-step, cisplatin will be given as follows: Step 1, 2 and 3: 50 mg/ m2 days 43, 50; 40 mg/m2 day 64.

Vinorelbine will be escalated in three steps:

Step 1: 10 mg/ m2 days 43, 50; 8 mg/m2 days 66 and 73. Step 2: 20 mg/ m2 days 43, 50; 8 mg/m2 days 66 and 73. Step 3: 20 mg/ m2 days 43, 50; 15 mg/m2 days 66 and 73.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed non-small cell lung cancer

• Inoperable stage III (UICC 2002; sixth edition) (no pleural effusion)

• WHO performance status 0 or 1

• Less than 10% weight loss in the last 6 months

• Lung function: FEV1 at least 50% and DLCO at least 50% of the predicted value

• No recent severe cardiac disease

• Adequate bone marrow function

• Adequate renal function

• Adequate hepatic function

• Life expectancy more than 6 months

• Measurable cancer

• Willing and able to comply with study prescriptions

• 18 years or older

• Not pregnant or breast feeding

• Written informed consent

• No previous radiotherapy to the chest

Exclusion Criteria:

• Not non-small cell lung cancer histology

• Mixed pathology

• History of prior chest radiotherapy

• Recent (<3 months) myocardial infarction

• Uncontrolled infectious disease

• Less than 18 years old

• Inadequate pulmonary function

• Other active malignancy

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Drug:
• Cetuximab
Eligible patients will be given 2 cycles(of 21 days) of carboplatin (AUC 5) day 1 and gemcitabine (1250 mg/m2) days 1,8. Patients without progressive disease will be entered in the phase I dose-escalation part of the study. Chest radiation will be given concurrently with cetuximab, cisplatin and vinorelbine, which will be escalated in 3 steps until dose-limiting toxicity occurs. 14 days after the last gemcitabine (=day 43), radiotherapy is started : First 3 weeks: 1.5 Gy BID to a dose of 45 Gy in 30 fractions, then 2 Gy QD to a mean lung dose of 19 Gy. Cetuximab: 400 mg/m2 7 days before radiotherapy (= day 36) and during the course of radiotherapy a weekly dose 250 mg/m2. Cetuximab will be delivered at the same days as chemotherapy. Cisplatin(all steps): 50 mg/m2 days 43, 50; 40 mg/m2 day 64. Vinorelbine: Step 1: 10 mg/ m2 days 43, 50; 8 mg/m2 days 66 and 73. Step 2: 20 mg/ m2 days 43, 50; 8 mg/m2 days 66 and 73. Step 3: 20 mg/ m2 days 43, 50; 15 mg/m2 days 66 and 73.

Locations

Country	Name	City	State
Netherlands	Maastricht Radiation Oncology, MAASTRO clinic	Maastricht	Limburg

Sponsors (3)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology	Academisch Ziekenhuis Maastricht, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation		3 months
Secondary	During and after chemo-radiation: (CTC 3.0) Dysphagia, Cough, Dyspnea, Skin rash, Myelitis, Neuropathy, Neutrophiles, Platelets, Hemoglobin, Diarrhea, Renal failure, Liver dysfunction, Tumour response 3 m. after end chemo-radiation and Survival		3 months